tbuckley/cabot-search huggingface dataset:
Sun exposure and associated risks: Insight from an international survey with a focus on the population with past medical history of skin cancers.
Authors: Brigitte Dreno, Thierry Passeron, Susana Puig, Cl Goh, Henry Lim, Fatimata Ly, H. Kang, A. Morita, Jorge Ocampo, Sergio Schalka, L. Wei, Caroline Lefloch, Anne-Laure Demessant, Delphine Kerob, Jean Krutmann
Journal: Journal of Clinical Oncology (2023)

e21575 Background: This survey investigates knowledge and behaviors regarding sun exposure among population who have been treated for skin cancer (melanoma/non melanoma) or pre-cancerous lesions in 17 countries. Methods: The survey (N = 17,001) was conducted online in 17 countries (5 continents) from 28 September-18 October 2021. Automated selection from the Ipsos online Panel ensured samples of 1,000 individuals in each country fit the quotas method based on gender, age, employment status, and country regions. Data covered demographics, phototype, exposure habits and practices, knowledge and understanding of risks. The current focus in this abstract was defined as individuals with a history of melanoma/non melanoma skin cancer, pre-cancerous lesions. Results: This sub population represents 8% of the general population (n = 1372), it comprised 54% men, average age was 49.9 years (SD:17.6) and 58% were of phototype 1-2. 90% were aware of sun-related skin-health issues (vs 88% in the general population). 79% did know that sun protection is useful when the weather is overcast, a better knowledge compared to the general population (61%). However, 34% indicated it was safe to expose themselves without protection when already tanned, a larger misconception compared to the general population (23%). 54% did not understand the difference between UVA and UVB vs 70% in the general population. Only 28% systematically/often use all protections measures during exposure; still a higher practice compared to the general population (12%). However, 42% said they protected from the sun all year round, a better habit compared to the general population (23%). During sun exposure, among the 91% who declared using sunscreen, 74% applied sunscreen only once or twice a day, a similar practice among general population (74%). And when already tanned 38% decreased frequency of application and/or used lower protection (44% among general population). 82% regretted not having previously used better protection, a much stronger regret compared to the general population (57%). Conclusions: Although individuals who have been treated for skin cancer or pre-cancerous lesions had better knowledge and behavioral attitudes compared to the general population, this survey shows that even a population at high risk of melanoma and having a regular medical follow-up does not sufficiently perceive the importance of photoprotection in a prevention objective. This leads to discuss the implementation of new information tools with more impact.
Utility of multi-gene panel-based germline analysis following genomic profiling and cascade testing in advanced solid tumors: An initial report of the BRANCH study.
Authors: Takeshi Kuwata, Yoshiaki Nakamura, Tomohiro Nishina, Naoki Takahashi, Hiroto Narimatsu, Hourin Cho, Chiaki Inagaki, Shigenori Kadowaki, Yoshinaga Okugawa, Sawako Matsuzaki, Naohiro Tomita, Hisateru Yasui, Yu Sunakawa, Manami Matsukawa, Kaori Kimura, Yumie Hiraoka, Makoto Hirata, Issei Imoto, Shinji Kosugi, Takayuki Yoshino
Journal: Journal of Clinical Oncology (2023)

10615 Background: Genetic testing for pathogenic germline variants (PGVs) is performed to identify hereditary cancer syndromes (HCS) and to evaluate the application of targeted therapies in clinical oncology. Multi-gene panels (MGPs) have become popular for identifying HCS; however, their clinical utility in therapeutic applications and confirmatory germline testing for presumed PGVs and in cascade testing are not well established. Methods: BRANCH [UMIN000046085] is a multicenter clinical study to confirm PGVs in: i) patients with advanced solid tumors in whom a presumed PGV has been detected by comprehensive genomic profiling (CGP) (cohort A); ii) patients who received a germline BRCA (gBRCA) test (cohort D); and iii) first-degree relatives of patients with PGVs identified in this study (cohort C). PGVs were examined in 35 HCS genes using an MGP combined with digital multiple-ligation-dependent probe amplification. Results: MGP results were available for 75 patients in cohort A and 83 in cohort D (3 February 2023). The most common cancer in cohort A was colorectal cancer (13%) followed by ovarian (12%) and breast (11%) cancers. Of 103 tested presumed PGVs, 46 (45%) were confirmed as PGVs, with the highest germline conversion rates in BRCA1 (8/8, 100%), followed by PALB2 (5/6, 83%) and BRCA2 (15/19, 79%) among the genes tested in ≥3 patients. In tissue-based CGP, true PGVs had a higher variant allelic frequency (median 55.7% [range, 31.9-96.8]) than non-PGVs (37.0% [9.3-86.9]). In cohort D, 61 (74%) patients had breast cancer, including one with both breast and ovarian cancers. All BRCA PGVs identified by gBRCA test were identified by MGP in 28 BRCA-positive patients. Intriguingly, among 55 patients (66%) in whom no BRCA PGV was detected by gBRCA test, non-BRCA PGVs were identified in 6 (11%) patients (2 PALB2 and 1 each of ATM, CHEK2, MSH2 [large deletion], and TP53). Thirty relatives in 18 pedigrees received MGP-based cascade testing in cohort C. The most frequent target genes were BRCA2 followed by BRCA1 and PALB2. The same PGVs as the probands were confirmed in 11 (37%) individuals and novel PGVs were identified in 2 (7%) relatives, leading to double PGVs in homologous recombination genes ( PALB2+ BRCA2 and BRCA2+ ATM), respectively . Conclusions: MGP successfully determined germline variants among presumed PGVs identified by CGP in patients with advanced solid tumors, and detected non-BRCA PGVs in 10% of gBRCA-negative patients. Furthermore, MGP-based cascade testing has the potential to identify other PGVs in addition to those detected in the probands. Clinical trial information: UMIN000046085 .
Analysis of tumor- and circulating-free DNA methylation to identify clinically relevant small cell lung cancer subtypes.
Authors: Simon Heeke, Carl Michael Gay, Marcos Roberto Estecio, Hai T. Tran, Benjamin B. Morris, Bingnan Zhang, XiMing Tang, Maria G Raso, Pedro Rocha, Edurne Arriola, Paul Hofman, Prasad Kopparapu, Christine M. Lovly, Kyle Concannon, Yuanxin Xi, Lixia Diao, Qi Wang, Jing Wang, Lauren Averett Byers, John Heymach
Journal: Journal of Clinical Oncology (2023)

8577 Background: Small-cell lung cancer (SCLC) is an aggressive malignancy composed of distinct transcriptional subtypes, defined by the predominant expression of one of the three transcription factors ASCL1 (SCLC-A), NEUROD1 (SCLC-N) and POU2F3 (SCLC-P) as well as an inflamed subtype (SCLC-I; see Gay et al. Cancer Cell. 2021), each with potential therapeutic vulnerabilities. Implementing subtyping in the clinic has remained challenging due to limited tissue availability, particularly for longitudinal monitoring. Given the known epigenetic regulation of critical SCLC transcriptional programs, we hypothesized that there would be subtype-specific patterns of DNA methylation that could be detected in tumor or blood from SCLC patients. Methods: We included 179 patients with SCLC and performed RNA sequencing and genomic-wide reduced-representation bisulfite sequencing (RRBS). We further analyzed DNA methylation in 68 plasma samples including longitudinal samples to track SCLC subtype evolution over time. Results: Using machine learning approaches, we developed a highly accurate DNA methylation-based classifier (SCLC-DMC) that could distinguish SCLC subtypes using clinical tumor samples with 95.8% accuracy in the testing set compared to mRNA-based profiling. We further adjusted the classifier for circulating-free DNA (cfDNA) to subtype SCLC from plasma. Using the cfDNA classifier (cfDMC), we could demonstrate that SCLC subtypes evolve frequently during disease progression, highlighting the need for longitudinal tracking of SCLC during clinical treatment. Furthermore, methylation-based subtyping predicted response to a wide variety of drugs in preclinical models like CDK and AURK inhibitors, and clinical outcomes were indistinguishable in cohorts of patients subtyped using mRNA or SCLC-DMC (p = 0.95). Conclusions: These data establish that tumor and cfDNA methylation can be used to identify SCLC subtypes and guide precision SCLC therapy.
Decomposing racial differences in financial hardship among older cancer survivors.
Authors: Elizabeth Davis, Alaina Yarbro, Smita Bhatia, Kelly Kenzik
Journal: Journal of Clinical Oncology (2023)

6598 Background: Despite Medicare coverage, financial hardship is a prevalent issue among older cancer survivors, particularly among those belonging to a racial/ethnic minority. Sociodemographic, clinical, and area-level factors may mediate this relationship; however, no studies have assessed the extent to which these factors contribute to disparities. Methods: Surveys assessing financial hardship after cancer were completed by 721 patients age 65y+ of Black or white race completing primary cancer treatment for breast, prostate, colorectal, prostate cancer or lymphoma at University of Alabama at Birmingham between 2000 and 2019. Financial hardship included material, psychological, and behavioral domains. Material hardship included ever 1) borrowing money/going into debt, 2) filed for bankruptcy, 3) worried about paying large medical bills, and 4) made any other financial sacrifices due to cancer. Psychological hardship was measured by asking if participants were ever worried about paying large medical bills related to cancer, its treatment or effects of treatment. Behavioral hardship was measured by asking if participants were unable or delayed in obtaining medical care, tests, treatments or prescriptions in the last 6 months. Non-linear Blinder-Oaxaca effect decomposition methods evaluated the extent to which individual-level sociodemographic, clinical, and area-level factors contributed to racial disparities in financial hardship. Results: Median age at survey was 78 (IQR = 73-82), majority were female (53%) and non-Hispanic White (84%). The most common cancers were breast (34%) and prostate (27%), followed by lung (17%), lymphoma (9%) and colorectal (14%). Ninety percent were diagnosed at an early stage and median time from diagnosis to survey was 8y (IQR = 5-12). There were no significant clinical differences between Black and white patients. Overall, 22% reported any financial hardship; 14% material, 3% behavioral, and 14% psychological. Black, compared to White participants reported significantly (p &lt; 0.001) higher rates of overall (39% v 18%), material (29% v 11%), and psychological (27% v 11%) financial hardship. Notably, Black patients had higher rates of being unable to cover cancer-related costs (23% v 7%), worrying about paying large medical bills (27% v 11%), and having to borrow money or go into debt (9% v 3%). Overall, the observed characteristics explained 81% of racial differences in financial hardship among cancer survivors, primarily by differences in income (24%), cancer diagnosis and stage (22%), and area deprivation (15%). Conclusions: These results identify primary contributors to racial disparities in financial hardship among older cancer survivors, which can be used to develop interventions aimed at eliminating inferior healthcare outcomes experienced by certain racial groups, inform policy, and allocate resources to those at greatest risk for financial hardship.
Mapping objectives of a new interprofessional morbidity and mortality conference to ACGME core competencies in hematology/oncology.
Authors: Aditya Sharma, Natasha Dhawan, Christi Ann Hayes, Katherine C Silvius, Frederick Lansigan
Journal: Journal of Clinical Oncology (2023)

11032 Background: Safety and quality improvement requirements are a part of the core competencies for ACGME-accredited hematology/oncology fellowships. The morbidity and mortality conference (MM) is a tool that has been used to identify safety issues and areas for improvement. The traditional format primarily includes an audience of clinicians. We sought to develop an interactive, interprofessional MM (i-MM), including institutional leadership, physicians, fellows, residents, advanced practice providers, nursing, and pharmacy, while meeting the ACGME Core competencies for Patient Safety and Quality Improvement in Hematology and Medical Oncology. Methods: A pilot i-MM was designed to create an enriching, interprofessional discussion regarding patient safety and quality improvement. We implemented a Plan-Do-Study-Act (PDSA) design to create the i-MM model that map to the core competencies. The first session was focused on two mortality events in immunocompromised hosts that triggered the sepsis bundle, one of which was due to toxic megacolon. The i-MM objectives were aligned with ACGME hematology/oncology fellowship requirements of quality and safety. The effectiveness of the pilot session was gauged via an anonymous post-session survey using a 4-point Likert scale. Results: A total of 32 people attended the pilot i-MM, including quality and safety leaders, faculty, fellows, medical residents, pharmacy, and nursing. A total of 10 participants across professions completed the post-i-MM survey. The survey demonstrated an average of 3.8/4 for all interprofessional educational goals, which included demonstration of mutual respect between healthcare professionals, engaging in effective interprofessional communication, and working within an interprofessional team. Content-specific aspects of the survey were rated with an average effectiveness of 3.60/4. Feedback on the survey recommended limiting i-MM to one case presentation instead of multiple. During the debrief session, it was reported that several nurses felt the moderated session was “inclusive and empowering”. Conclusions: The i-MM was an effective approach to meeting ACGME requirements for safety and quality learning objectives while creating an inclusive environment for all team members. Future PDSA cycles will continue to map i-MM learning objectives to ACGME hematology/oncology fellowship program core competencies in Section VI.A.1 and the section on Professionalism. Core competency mapping will guide future presentations that address issues on quality, safety, and health care disparities. Specific presenters and moderators from different professions will be chosen to lead each i-MM, with the goal of examining each case from different perspectives to provide a holistic interprofessional view of delivering quality medical care to patients.
Web-based patient-reported outcome measures (PROMs) in elderly cancer patients: A French multicentric prospective feasibility trial (the FASTOCH study).
Authors: Mathilde Cancel, Carine Sauger, Julie Biogeau, Véronique Dardaine, Thierry Lecomte, Amandine Deloigne, Philippe Hebrard, Rémy Wilmet, David Solub, François Christiann, Philippe Laplaige, Pierre Combe, Etienne Dorval
Journal: Journal of Clinical Oncology (2023)

12011 Background: Web-based PROMs in cancer care improve overall survival and quality of life. There is, nonetheless, no data available on this type of follow-up in the elderly population. Methods: From February 2021 to April 2022, 75 or more years-old patients ongoing any active anti-cancer treatment (such as chemotherapy, targeted therapy, hormonotherapy, immune therapy) were included, in six French cancer centers. Feasibility of the web-based PROMs was assessed as the part of the population included that could use the Ana-Health’s web-based application “ANA” to monitor their symptoms, the others being considered as in “primary failure” due to technological barriers or refusal to participate. Among the patients that agreed to participate, we then defined as “active” those who filled at least one form during the three months follow up. We also searched for factors restraining elderly patients to use “ANA” and evaluated their satisfaction. Results: Overall, 473 patients were included in the study. There were 288 patients in “primary failure” (233 without Internet access, 17 not comfortable enough to use web-based PROMs, 38 refusals to participate). Among the 185 patients “willing to participate”, there were 122 “active” patients and 63 “inactive” ones, leading to a 26% feasibility in intention-to-test and a 66% feasibility in per protocol analysis. Patients “willing to participate” were from higher socio-professional category (p = 0.002) and had a significantly higher G8 score (13.5 versus 12, p &lt; 0.001), particularly when considering the autonomy (p = 0.028), cognitive assessment (p = 0.003) and general condition (p &lt; 0.001) items. In the multivariate analysis, the socio-professional category and the general condition were still significantly different (p = 0.009 and 0.002 respectively). The only factor that remained significantly different between the “active” and “inactive” populations was the better general condition in the “active” group (p &lt; 0.001). The “inactive” patients prematurely ended their participation because they lost interest in the web-based follow up significantly more than the “active” group (28 “inactive” patients, i.e. 44%, vs 5 “active” patients, i.e. 4%, p &lt; 0.001). Similarly, the “active” patients were significantly more satisfied with “ANA” than the “inactive” (71% vs 29%, p &lt; 0.001). Conclusions: Our study shows that, in the elderly population treated for a cancer, a web-based application to measure PROs is feasible, however socio-professional category, general condition and above all technological barriers are of some concern.
Biomarker testing and treatment patterns in US patients (pts) with advanced/metastatic non-small cell lung cancer (NSCLC) harboring <i>MET</i> amplification.
Authors: Alex Ryder, Dina Oksen, Emmanuelle Boutmy, Yuexi Wang, Alnecia R. Nisbett, Christopher Stroh, Andreas Johne
Journal: Journal of Clinical Oncology (2023)

e21057 Background: Limited published evidence exists on pts with advanced stage NSCLC harboring MET amplification ( METamp), a rare oncogenic driver. We report here real-world biomarker testing and treatment patterns for these patients. Methods: This was a non-interventional, descriptive cohort study using ConcertAI electronic medical record data derived from US community oncology centers and linked with ASCO/CancerLinQ data. Eligible pts had stage IIIB–IV NSCLC and METamp. Study period: Jan 1, 2004 – Oct 31, 2021. Results: Of 8,454 lung cancer pts with minimum 1 molecular test including MET, 164 had METamp (1.9%). Pts were mainly identified from 2015 onwards and primarily in oncology in the Southern and Midwest regions (86.6%). Majority of pts were tested by tissue biopsy (67.1%), 20.7% by liquid biopsy and 12.2% not specified. At least 64.5% of pts were highly MET amplified (either gene copy number ≥8 or by liquid biopsy ++, +++). Other mutations screened for were ALK, ROS1 and EGFR (99.4%, 98.2% and 97.6%), with oncogenic ALK, ROS1 fusions and activating EGFR mutations in 0.6% and 13.1%, respectively. BRAF and KRAS were less frequently screened for (90.2% and 87.2%), with potential oncogenic alterations in 2.0% and 12.6%. Of 127 pts tested for PD-L1 (by immunohistochemistry), 63.0% were positive, and 72.5% had tumor proportion score ≥50. Eighteen pts had METamp detected after receiving an EGFR tyrosine kinase inhibitor (TKI), indicating METamp as a secondary oncogenic driver. RB1 loss and MYC amplification, as potential mechanisms of MET inhibition resistance, were not frequently screened for (30.5% and 46.3%). RB1 loss was identified in 2.0% and MYC amplification in 15.8%. Next generation sequencing was the most frequent diagnostic used overall. A total of 144 pts (87.8% of 164 pts) received first-line (1L) anticancer therapy; platinum-based chemotherapy 57/144 (39.6%), immune-checkpoint inhibitors 50/144 (34.7%) or EGFR TKI monotherapy 24/144 (16.7%), other 2/144 (1.4%) and MET TKIs (mainly crizotinib) were used in 11/144 pts (7.6%) in 1L, 14/78 (17.9) in second line and 7/42 (16.7%) in third line. Conclusions: In this cohort of pts identified in a US community oncology setting, biomarker screening even for rarer genetic alterations occurred. Concomitant genetic alterations to METamp were infrequent except for alterations of EGFR and KRAS. The frequency of pts with high level of METamp in the cohort may explain the lower frequency of other biomarkers, as high level of amplification indicates a cleaner MET profile. Overall MET inhibitor treatment was not common. Screening for novel and rare biomarkers such as METamp as a primary or secondary oncogenic driver is becoming increasingly important to enable efficacious targeted treatment.
A matching-adjusted indirect treatment comparison of elranatamab in patients with triple-class exposed relapsed/refractory multiple myeloma: Comparisons with belantamab mafodotin, selinexor plus dexamethasone, and real-world physician’s choice of treatment.
Authors: Patrick Hlavacek, Isha Mol, Yannan Hu, Joseph C. Cappelleri, Haitao Chu, Didem Aydin
Journal: Journal of Clinical Oncology (2023)

e20038 Background: Elranatamab, a bispecific antibody targeting B-cell maturation antigen on multiple myeloma (MM) cells and CD3 on T cells, is being evaluated as a monotherapy in the MagnetisMM-3 trial (MM3; NCT04649359) in patients with triple-class exposed (TCE) relapsed/refractory MM. While there is no standard of care for TCE MM, belantamab mafodotin (belamaf) and selinexor plus dexamethasone (sel-dex) are treatment options. LocoMMotion is a prospective, non-interventional study investigating real-world physician’s choice of treatment (PCT) in patients with TCE MM. In the absence of head-to-head trials, unanchored matching-adjusted indirect comparisons (MAIC) were conducted to compare the relative efficacy across comparators. Methods: Individual patient-level data were obtained for elranatamab from MM-3 (data cut Oct 2022). Aggregated data for belamaf, sel-dex, and PCT were obtained from DREAMM-2 (NCT03525678), STORM (NCT02336815), and LocoMMotion (NCT04035226). Unanchored MAICs were conducted to compare the relative treatment effect on objective response rate (ORR) accounting for potential different distributions of prognostic variables (PVs) and effect modifiers (EMs). In the base case, PVs identified via logistic regressions based on MM-3 data were adjusted. In sensitivity analyses, PVs/EMs identified from the literature were added. Relative treatment effects were measured by rate differences and odds ratios. Results: After MAIC adjustments, the selected PVs/EMs were balanced in each comparison. The table presents the results from the naïve comparison with no MAIC adjustment plus the MAIC base case. The ORR of elranatamab was statistically higher than belamaf, sel-dex, and PCT in LocoMMotion. Results were consistent across all sensitivity analyses. Conclusions: Elranatamab had a significantly higher ORR than belamaf, sel-dex, and real-world PCT in LocoMMotion for patients with TCE MM, demonstrating its clear clinical benefit for this population. [Table: see text]